Abstract: The blockade of targeted immune checkpoint is one of the most promising approaches to activate therapeutic antitumor immunity. The immune checkpoint refers to a plethora of inhibitory pathways in the immune system. These pathways are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues to minimize collateral tissue damage. Tumors co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance. Cytotoxic T-lymphocyte-associated antigen 4 antibodies were the first of this class of immunotherapeutics to acquire approval from the US Food and Drug Administration. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1, indicate broad and diverse opportunities to enhance anti-tumor immunity with the potential to produce durable clinical responses. Classic chemotherapy exerts significant immunomodulatory effects on tumor cells via multiple mechanisms. Therefore, the combination of immunotherapy, including immune checkpoint blockade with chemotherapy, is a new promising trend in anti-tumor immunotherapy.